The preservation of bidirectional promoter architecture in eukaryotes: what is the driving force?

BackgroundThe bidirectional gene architecture has been studied in many organisms, and the conservation of bidirectional arrangement has received considerable attention. However, the explanation for the evolutionary conservation about this genomic structure is still insufficient. In this study the large scale identification and pathway enrichment analysis for bidirectional genes were performed in several eukaryotes and the comparative analysis of this arrangement between human and mouse were dissected for the purpose of discovering the driving force of the preservation of this genomic structure.ResultsWe identified the bidirectional gene pairs in eight different species and found this structure to be prevalent in eukaryotes. The pathway enrichment analysis indicated the bidirectional genes at the genome level are conserved in certain pathways, such as the DNA repair and some other fundamental cellular pathways. The comparative analysis about the gene expression, function, between human and mouse bidirectional genes were also performed and we observed that the selective force of this architecture doesn't derive from the co-regulation between paired genes, but the functional bias of bidirectional genes at whole genome level is observed strengthened during evolution.ConclusionsOur result validated the coexpression of bidirectional genes; however failed to support their functional relevance. The conservation of bidirectional promoters seems not the result of functional connection between paired genes, but the functional bias at whole genome level, which imply that the genome-wide functional constraint is important for the conservation of bidirectional structure.

[1]  F. Baas,et al.  The Human Transcriptome Map: Clustering of Highly Expressed Genes in Chromosomal Domains , 2001, Science.

[2]  E. Levanon,et al.  Human housekeeping genes are compact. , 2003, Trends in genetics : TIG.

[3]  Hiroyuki Ogata,et al.  KEGG: Kyoto Encyclopedia of Genes and Genomes , 1999, Nucleic Acids Res..

[4]  M. Lieber,et al.  Bidirectional Gene Organization A Common Architectural Feature of the Human Genome , 2002, Cell.

[5]  Benjamin M. Bolstad,et al.  affy - analysis of Affymetrix GeneChip data at the probe level , 2004, Bioinform..

[6]  Leighton J. Core,et al.  Divergent transcription: A new feature of active promoters , 2009, Cell cycle.

[7]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[8]  Andrew M. Jenkinson,et al.  Ensembl 2009 , 2008, Nucleic Acids Res..

[9]  Gene W. Yeo,et al.  Divergent Transcription from Active Promoters , 2008, Science.

[10]  Christophe Malabat,et al.  Widespread bidirectional promoters are the major source of cryptic transcripts in yeast , 2009, Nature.

[11]  Hui Yu,et al.  Systematic Analysis of Head-to-Head Gene Organization: Evolutionary Conservation and Potential Biological Relevance , 2006, PLoS Comput. Biol..

[12]  Gerald M Rubin,et al.  Evidence for large domains of similarly expressed genes in the Drosophila genome , 2002, Journal of biology.

[13]  Martin J Lercher,et al.  Genomic regionality in rates of evolution is not explained by clustering of genes of comparable expression profile. , 2004, Genome research.

[14]  Martin J. Lercher,et al.  Clustering of housekeeping genes provides a unified model of gene order in the human genome , 2002, Nature Genetics.

[15]  Junjun Zhang,et al.  BioMart Central Portal—unified access to biological data , 2009, Nucleic Acids Res..

[16]  Jiajia Chen,et al.  Genome-wide analysis of the transcription factor binding preference of human bi-directional promoters and functional annotation of related gene pairs , 2011, BMC Systems Biology.

[17]  Peer Bork,et al.  Similar gene expression profiles do not imply similar tissue functions. , 2006, Trends in genetics : TIG.

[18]  J. Simonoff Smoothing Methods in Statistics , 1998 .

[19]  Leighton J. Core,et al.  Nascent RNA Sequencing Reveals Widespread Pausing and Divergent Initiation at Human Promoters , 2008, Science.

[20]  Rafael A Irizarry,et al.  Exploration, normalization, and summaries of high density oligonucleotide array probe level data. , 2003, Biostatistics.

[21]  R. Myers,et al.  An abundance of bidirectional promoters in the human genome. , 2003, Genome research.

[22]  Mary Yang,et al.  Comparative analyses of bidirectional promoters in vertebrates , 2008, BMC Bioinformatics.

[23]  A. Bird,et al.  Gene number, noise reduction and biological complexity. , 1995, Trends in genetics : TIG.

[24]  Ben-Yang Liao,et al.  Erratum: Impacts of gene essentiality, expression pattern, and gene compactness on the evolutionary rate of mammalian proteins (Molecular Biology and Evolution (2006) 23, (2072-2080) DOI: 10.1093/molbev/msl076) , 2007 .

[25]  W. Kamps,et al.  Evidence Based Selection of Housekeeping Genes , 2007, PloS one.

[26]  Sampsa Hautaniemi,et al.  Fast Gene Ontology based clustering for microarray experiments , 2008, BioData Mining.

[27]  S. Batalov,et al.  A gene atlas of the mouse and human protein-encoding transcriptomes. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Ben-Yang Liao,et al.  Impacts of gene essentiality, expression pattern, and gene compactness on the evolutionary rate of mammalian proteins. , 2006, Molecular biology and evolution.

[29]  T. Ryan Gregory,et al.  Eukaryotic genome size databases , 2006, Nucleic Acids Res..

[30]  Takeshi Itoh,et al.  Comparative genomics of bidirectional gene pairs and its implications for the evolution of a transcriptional regulation system. , 2005, Gene.

[31]  K. H. Wolfe,et al.  Eukaryote genome duplication - where's the evidence? , 1998, Current opinion in genetics & development.

[32]  E. Birney,et al.  EnsMart: a generic system for fast and flexible access to biological data. , 2003, Genome research.

[33]  T. Andrews,et al.  The Ensembl automatic gene annotation system. , 2004, Genome research.

[34]  Quan Wang,et al.  Searching for bidirectional promoters in Arabidopsis thaliana , 2009, BMC Bioinformatics.

[35]  Thomas Blumenthal,et al.  Coexpression of neighboring genes in Caenorhabditis elegans is mostly due to operons and duplicate genes. , 2003, Genome research.